Prospective study of MMP7 serum levels in the diagnosis of cholangiocarcinoma

Table 1 Clinical characteristics of patients with benign biliary tract diseases (control) and cholangiocarcinoma

	Control	Cholangiocarcinoma	P
	n = 128	n = 59
Age (yr)	61 ± 7	67 ± 5	0.451
Sex (M:F)	62:66	36:23	0.118
Albumin (mg/dL)	3.9 ± 0.67	3.1 ± 0.59	< 0.001
Globulin (mg/dL)	3.9 ± 0.72	4.1 ± 0.91	0.073
Total bilirubin (mg/dL)	3.3 ± 3.71	12.0 ± 11.35	< 0.001
AST (U/L)	73.4 ± 78.14	91.2 ± 75.91	0.003
ALT (U/L)	76.3 ± 83.32	52.2 ± 43.58	0.884
ALP (U/L)	320.3 ± 230.03	380.5 ± 314.52	< 0.001

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase.

Table 2 Performance of the biomarkers for the diagnosis of cholangiocarcinoma (%) (95% CI)

Tumor markers (cut-off value)	Sensitivity	Specificity	PPV	NPV	LR+	LR-
MMP7 (5.5 ng/mL)	75 (63-86)	78 (71-85)	61 (50-72)	87 (81-93)	3.41 (2.38-4.89)	0.33 (0.21-0.51)
MMP7 (6.5 ng/mL)	63 (50-75)	87 (81-93)	69 (56-81)	83 (77-90)	4.72 (2.91-7.66)	0.43 (0.31-0.60)
MMP7 (7.5 ng/mL)	53 (40-65)	92 (88-97)	76 (62-89)	81 (74-87)	6.73 (3.54-12.70)	0.51 (0.39-0.68)
CA19-9 (35 U/mL)	71 (60-83)	73 (66-81)	55 (44-66)	85 (78-91)	2.68 (1.93-3.73)	0.39 (0.26-0.59)
CA19-9 (100 U/mL)	68 (56-80)	87 (81-93)	70 (58-82)	85 (79-91)	5.1 (3.17-8.22)	0.37 (0.25-0.54)
CA19-9 (200 U/mL)	59 (47-72)	93 (89-97)	80 (68-91)	83 (77-89)	8.44 (4.34-16.40)	0.44 (0.32-0.60)

PPV: Positive predictive value; NPV: Negative predictive value; LR+: Positive likelihood ratio; LR-: Negative likelihood ratio; CI: Confidence interval; MMP7: Matrix metalloproteinase-7; CA19-9: Carbohydrate antigen 19-9.

Table 3 Predicted probability of the combination of serum carbohydrate antigen 19-9 and matrix metalloproteinase-7 for diagnosis of cholangiocarcinoma

CA19-9 (> 100 U/mL)	MMP7 (> 5.5 ng/mL)	Predicted probability (%)
-	-	6.40
-	+	36.10
+	-	42.84
+	+	86.12

MMP7: Matrix metalloproteinase-7; CA19-9: Carbohydrate antigen 19-9.

Table 4 Pearson’s correlation coefficients of matrix metalloproteinase-7, carbohydrate antigen 19-9, albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase

Pearson correlation	CA19-9	Albumin	Total bilirubin	AST	ALT	ALP
MMP7	0.415a	-0.577a	0.328a	0.154a	-0.055	0.268a
CA19-9	0.415a	-0.370a	0.356a	0.064	-0.022	0.139

^aStatistically significant, P < 0.05. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; MMP7: Matrix metalloproteinase-7; CA19-9: Carbohydrate antigen 19-9.

Table 5 Odd Ratios estimates for diagnosis of cholangiocarcinoma

Variables	OR (95% CI)	P
CA19-9	15.2 (5.20-44.56)	< 0.001
MMP7	5.5 (1.87-16.03)	0.002
Albumin	0.015 (0.01-0.15)	< 0.001
Total bilirubin	2.4 (0.81-7.20)	0.115
AST	1.2 (0.37-4.12)	0.738
ALP	0.3 (0.09-1.05)	0.060

The significant parameters (P < 0.05) selected by the model are shown. AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; MMP7: Matrix metalloproteinase-7; CA19-9: Carbohydrate antigen 19-9.